To maintain and build on the Sidney Kimmel Comprehensive Cancer Centers (SKCCC) record of excellence in the fields of cancer genetics and epigenetics, the SKCCC established a new Next Generation Sequencing Core (NGSC) as a shared resource in January 2009. A product of a convergence of advances in molecular biology, engineering, computer science, and bioinformatics. Next Generation Sequencing features the ability to sequence billions of base pairs of DNA in a single run, at a cost that is several orders of magnitude less than previous gold standard sequencing technologies. Next Generation Sequencing is an extremely versatile technology and can be used to investigate a multitude of genomic processes in a previously unimaginable genome-wide and unbiased fashion. In order to facilitate widespread adoption of this relatively new technology, rather than administering the Core as a black-box facility, the Core operates as a collaborative Core in which users can consult and collaborate with NGSC faculty and staff to: 1) identify the optimal molecular biology approaches (prior to sequencing library construction) to synapse their research questions with the capabilities of the Core, 2) prepare the appropriate libraries and carry out massively parallel sequencing, and 3) carry out the appropriate primary, secondary, and tertiary bioinformatics analyses to analyze and interpret the results. The NGSC features Applied Biosystems SOUD Next Generation Sequencing instruments capable of generating nearly 100 Gigabases of sequencing data in a single run, state-of-the-art equipment for sequencing library preparation and quality control, and powerful computational resources including a server with ten compute nodes (each containing Quad Core Intel Xeon processors and 16 Gigabytes of memory) and 100 terabytes of storage for dedicated bioinformatics analyses. The Core is currently administered by a faculty director overseeing all activities, a faculty Co-Director overseeing bioinformatics support, a laboratory manager, and a bioinformatics manager. The Core's goal is to be as flexible as possible in assisting researchers in exploring all aspects of cancer genetics and epigenetics, including, but not limited to, germline and somatic variation/mutation, genomic structural variations/alterations, transcriptome analysis, transcription factor binding sites, chromatin modifications, and DNA methylation. Lay: The Next Generation Sequencing Core provides cutting edge services that harness the most recent technological advances to allow large scale genomic sequencing of many hundreds of millions of DNA molecules in parallel at about 100,000 times less cost than previous sequencing technologies. These services are poised to rapidly accelerate the pace of discovery and clinical translation in cancer molecular genetics research. SKCCC Managed Shared Resource.